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Originally published November 21, 2024
Last updated November 21, 2024
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Lung cancer impacts more nonsmokers than smokers today. It’s been a growing trend for more than a decade.
“It’s a common misconception that lung cancer is a smoker’s disease,” says Graeme Rosenberg, MD, a thoracic surgeon with USC Surgery and the USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC. “In fact, I treat more nonsmoking lung cancer patients than smoking-related lung cancer patients these days.”
Despite lung cancer diagnoses rising in relatively young, healthy, nonsmoking adults — particularly women — few in this demographic are routinely screened for the disease. And because lung cancer often doesn’t present symptoms until its advanced stages, patients who do eventually develop the disease may not be diagnosed soon enough.
Unfortunately, when lung cancer cases are detected today in nonsmokers, it’s usually by accident — for instance, after a patient has CT screening for a different concern. “A lot of these masses are detected because a CT scan was obtained for another reason,” Rosenberg says.
Researchers are trying to ascertain who is at most risk of developing lung cancer, especially among nonsmokers. For instance, one demographic in which lung cancer is rising is young, nonsmoking Asian American women. An EGFR mutation, a gene mutation commonly linked to lung cancer, records higher rates in this demographic. This gene mutation is unrelated to any environmental risk factors, Rosenberg adds.
“This is a newer area of research, trying to determine what the clinical profile looks like,” Rosenberg says. The goal is to regularly screen patients at risk and detect lung cancer at its early stages, when it is most treatable. “We want to identify early-stage lung cancer before it spreads to the lymph nodes,” he says.
To do so, he adds, “We need to continue investigating the independent risk factors we can use to plan screening protocols.”
Without broader lung cancer screening, many at-risk nonsmokers may continue flying under the radar of detection.
By contrast, smokers, who are already on high alert for developing lung cancer, are preemptively screened. These patients are more often recommended for CT scans, per guidelines from the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network and the Society of Thoracic Surgeons, Rosenberg says.
“These guidelines recommend who should get a low-dose lung cancer screening CT scan — usually patients between the ages of 50 and 80 who have more than a 20-year history of smoking, are currently smoking or have smoked within the last 15 years,” he says.
The guidelines aren’t clear-cut in terms of which nonsmokers should be screened — and when. Currently, Rosenberg says, “some population health studies show that only a minority of eligible patients receive a screening CT scan for lung cancer.”
It remains to be seen whether the needle will move one day on screening. “It’s a population health question,” Rosenberg says. “How many CT scans would you need to perform to detect lung cancer in a low-risk population, meaning those who don’t have exposure to smoking or a family history of cancer? Determining that number is challenging. You’d have to do a lot of CT scans. The question is how do you identify who would be the person to most likely benefit from a CT scan? How do you choose which patients ‘deserve’ a screening CT scan?”
Increasing genetic mutation testing isn’t really a solution either, he adds, because genetic profiling is generally done on the cancer tumor itself once it’s already been found. “This means that a tumor has already been identified, and we’re outside the realm of screening,” he says.
The fortunate news is that once a patient is eventually diagnosed with lung cancer, there are more gene-specific medications being developed to target specific gene mutations. Sometimes these therapeutics can serve as the main treatment, without requiring a patient to have chemotherapy or radiation.
“There are a half dozen different targeted medications right now,” Rosenberg says. “They provide more options, increasing our armamentarium of medications that we can combine with local therapies such as surgical resection, chemotherapy or radiation.”
Analyzing a tumor’s genetic makeup is critical. “Once a tumor is diagnosed, it’s important to understand its genetic profiling because many of these tumors may harbor a mutation for which we do have a drug and that drastically improves disease control and prognosis going forward,” he explains. “This is why we routinely test either our biopsies or resection specimens with next-generation gene sequencing. This should be a priority for any clinic treating lung cancer.”
Tumor type also dictates treatment decisions, whether it’s small-cell lung cancer or non-small cell lung cancer, the two most common lung cancer types that are not metastatic lung cancers that have spread from elsewhere in the body. “These cancers are further categorized into adenocarcinoma and squamous cell carcinoma, each with its own tumor biology and prognostication response to various treatments,” Rosenberg explains. “The most typical lung cancer is adenocarcinoma non-small cell lung cancer. There is also another group of lung nodules called carcinoid tumors, which are neuroendocrine tumors that we can commonly see. They’re rarer, but we will see tumors of the lung or the airways that have a carcinoid tumor pathology.”
Other factors determining whether a patient could benefit from a gene-targeted therapeutic are tumor stage, size, grade-invasive features, margin status, lymph node status, as well as the patient’s age and other medical concerns.
Mapping out a treatment plan for lung cancer once diagnosed is complex specifically because there are numerous treatment pathways available.
“The question is no longer just about whether a patient gets chemotherapy or not,” Rosenberg explains. “Now we must understand if a patient would benefit from chemotherapy, immunotherapy or targeted novel medications directed towards a tumor-genetic mutation. For instance, there is a lot of clinical research taking place about who should get upfront chemotherapy and immunotherapy, or which tumors should be treated with what’s called perioperative chemo immunotherapy (a combination of chemotherapy and immunotherapy), followed by resection and then treatment after. And if an early-stage lung cancer has been detected, diagnosed and resected, with no concerning lymph node or tumor characteristics identified, it may just need surveillance.”
Making these decisions often takes input from numerous experts working collaboratively, such as at Keck Medicine, Rosenberg says.
Also, he adds, as soon as lung cancer is suspected, seeing a specialist is important. “If an abnormality is found on a patient’s imaging — imaging that was obtained for some other reason — you need either a thoracic surgeon, a pulmonologist or someone with expertise in lung pathology to help decide on next steps because these can be very complex. Should this be biopsied? How close in intervals should the CT scans be? Do you need a PET scan? Does the patient have any risk factors or prior medical history that would make us want to pursue scanning or a biopsy sooner?”
He adds that there are many randomized controlled trials in medical oncology looking at how to develop an individualized treatment plan for lung cancer patients and their tumor biology that will increase the odds of long-term survival and decrease risk of recurrence.
While great progress is being made in developing gene-specific drugs for lung cancer, more work needs to be done to develop more purposeful screening of nonsmokers and other patients not obviously at risk of the disease.
“Some other countries have developed lung cancer screening protocols for almost anybody,” Rosenberg concludes. “But in the U.S., there are currently no initiatives for screening protocols for nonsmokers. Right now, our only lung cancer screening pathway in the U.S. is for people who have a history of smoking. Will this change in the future? I think it could.”
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